The safety of systemic Janus kinase inhibitors in atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials

Janus kinase (JAK) inhibitors have been recently approved by the FDA and are widely used in the treatment of patients with atopic dermatitis. However, a comprehensive safety profile of JAK inhibitors in patients with atopic dermatitis has not been analysed. This study aimed to establish clinical evidence for the safety of systemic JAK inhibitors in patients with atopic dermatitis. Medline, Embase, , Cochrane Central Register of Controlled Trials (CENTRAL) and International Clinical Trials Registry Platform (ICTRP) were considered for search databases. Randomized controlled trials reporting the adverse events of systemic therapy in patients with atopic dermatitis were included. The risk of 11 adverse events was compared between the JAK inhibitors and placebo groups. Fourteen randomized controlled trials were analysed published between 2019 and 2022. The JAK inhibitors included in the analysis were abrocitinib (10, 30, 100 and 200 mg), baricitinib (1, 2 and 4 mg) and upadacitinib (7.5, 15 and 30 mg). The risk of herpes zoster, headache, acne, elevated blood creatinine phosphokinase and nausea was significantly increased, but the risk of serious infection, non-melanoma skin cancer (NMSC), malignancies other than NMSC, major adverse cardiovascular event, venous thromboembolism and nasopharyngitis was not increased. This study provides comprehensive clinical evidence on the risk of various adverse events in patients with atopic dermatitis. However, since the follow-up periods of the studies analysed in this review were mostly limited to 16 weeks or less, it is recommended that comprehensive long-term observational studies be conducted to determine any potential adverse events associated with major cardiovascular events or malignancies, which typically have prolonged courses.